Antagonistic lipopolysaccharides block E. coli lipopolysaccharide function at human TLR4 via interaction with the human MD-2 lipopolysaccharide binding site.

Antagonistic lipopolysaccharides block E. coli lipopolysaccharide function at human TLR4 via interaction with the human MD-2 lipopolysaccharide binding site. Research Abstract Details 

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Antagonistic lipopolysaccharides block E. coli lipopolysaccharide function at human TLR4 via interaction with the human MD-2 lipopolysaccharide binding site. Abstract Text:

Stephen R Coats,Christopher T Do,Lisa M Karimi-Naser,Pamela H Braham,Richard P Darveau,

Lipopolysaccharides containing underacylated lipid A structures exhibit reduced abilities to activate the human (h) Toll-like receptor 4 (TLR4) signalling pathway and function as potent antagonists against lipopolysaccharides bearing canonical lipid A structures. Expression of underacylated lipopolysaccharides has emerged as a novel mechanism utilized by microbial pathogens to modulate host innate immune responses. Notably, antagonistic lipopolysaccharides are prime therapeutic candidates for combating Gram negative bacterial sepsis. Penta-acylated msbB and tetra-acylated Porphyromonas gingivalis lipopolysaccharides functionally antagonize hexa-acylated Escherichia coli lipopolysaccharide-dependent activation of hTLR4 through the coreceptor, hMD-2. Here, the molecular mechanism by which these antagonistic lipopolysaccharides act at hMD-2 is examined. We present evidence that both msbB and P. gingivalis lipopolysaccharides are capable of direct binding to hMD-2. These antagonistic lipopolysaccharides can utilize at least two distinct mechanisms to block E. coli lipopolysaccharide-dependent activation of hTLR4. The main mechanism consists of direct competition between the antagonistic lipopolysaccharides and E. coli lipopolysaccharide for the same binding site on hMD-2, while the secondary mechanism involves the ability of antagonistic lipopolysaccharide-hMD-2 complexes to inhibit E. coli lipopolysaccharide-hMD-2 complexes function at hTLR4. It is also shown that both hTLR4 and hMD-2 contribute to the species-specific recognition of msbB and P. gingivalis lipopolysaccharides as antagonists at the hTLR4 complex.

Antagonistic lipopolysaccharides block E. coli lipopolysaccharide function at human TLR4 via interaction with the human MD-2 lipopolysaccharide binding site. Publishing Authors By Initials

SR Coats,CT Do,LM Karimi-Naser,PH Braham,RP Darveau,

For similar proteins: membrane proteins: receptors, cell surface: receptors, immunologic: receptors, pattern recognition: toll-like receptors: toll-like receptor 4 research abstracts see: proteins: membrane proteins: receptors, cell surface: receptors, immunologic: receptors, pattern recognition: toll-like receptors: toll-like receptor 4 research

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Antagonistic lipopolysaccharides block E. coli lipopolysaccharide function at human TLR4 via interaction with the human MD-2 lipopolysaccharide binding site. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Cellular microbiology

VOLUME: 9

Page Numbers: 1191-202

Journal Abbreviation:

ISSN: 1462-5814

DAY: 9

MONTH: 01

YEAR: 2007

Antagonistic lipopolysaccharides block E. coli lipopolysaccharide function at human TLR4 via interaction with the human MD-2 lipopolysaccharide binding site. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 100883691

Antagonistic lipopolysaccharides block E. coli lipopolysaccharide function at human TLR4 via interaction with the human MD-2 lipopolysaccharide binding site. Keywords Mesh Terms:

KEYWORDS: Toll-Like Receptor 4

MESH TERMS: metabolism

Chemical & Substance for Abstract: Antagonistic lipopolysaccharides block E. coli lipopolysaccharide function at human TLR4 via interaction with the human MD-2 lipopolysaccharide binding site. Information

Substance Name: Toll-Like Receptor 4

Registry Number: 0

Grant and Affiliation Information for Antagonistic lipopolysaccharides block E. coli lipopolysaccharide function at human TLR4 via interaction with the human MD-2 lipopolysaccharide binding site.

AFFILIATION: Department of Periodontics, University of Washington School of Dentistry, Seattle, WA 98195, USA. scoats@u.washington.edu

Country: England

AGENCY: United States NIDCR

GRANT: DE 13325

ACRONYM: DE

MEDLINETA: Cell Microbiol

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Antagonistic lipopolysaccharides block E coli lipopolysaccharide function at human TLR4 via interaction with the human MD-2 lipopolysaccharide binding site Related Publications

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• Antagonistic lipopolysaccharides block E. coli lipopolysaccharide function at human TLR4 via interaction with the human MD-2 lipopolysaccharide binding site.
• Hierarchical gene expression profiles of HUVEC stimulated by different lipid A structures obtained from Porphyromonas gingivalis and Escherichia coli.